A multicenter, open-label, expanded phase 2 study to evaluate the safety and efficacy of etirinotecan pegol, a polymer conjugate of irinotecan, in women with recurrent platinum-resistant or refractory ovarian cancer.

OBJECTIVE: Etirinotecan pegol (EP) is a novel polyethylene glycol conjugated form of irinotecan with documented activity in platinum-resistant ovarian cancer (PROC). We report the results of the expanded portion of a phase II study of EP in patients with PROC who received prior pegylated liposomal doxorubicin (PLD) or who were unable to receive it. METHODS: This multicenter, open-label, phase II study evaluated EP q21d for PROC. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors version 1.0. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Patient populations evaluated included a modified intent-to-treat (mITT) group consisting of all patients who received at least one dose and with measurable disease and a primary efficacy (pEFF) group (subset of the mITT population who received prior PLD). RESULTS: One hundred thirty-nine patients were enrolled. Of the 132 patients in the mITT group, 20 achieved an ORR (15.2%; 95% CI 9.5-22.4); median PFS and OS were 4.4 months and 10.2 months, respectively. In the pEFF group (n=104), 15 patients (14.4%; 95% CI 8.3-22.7) achieved an ORR; median PFS and OS were 4.4 months and 10.9 months, respectively. The most common grade 3/4 toxicities were diarrhea (20%), abdominal pain (17%), vomiting (14%), dehydration (13%), and nausea (13%). Severe diarrhea was reduced to 15% with strict adherence to screening and management guidelines. CONCLUSIONS: This study confirms the activity and safety of single-agent EP in patients with PROC, including patients who received prior PLD. Further evaluation earlier in the disease course and in combination is warranted.

A very rare case of vaginal angiokeratoma.

Angiokeratomas are benign, vascular lesions that are very rarely identified in the vagina. A patient originally presented with endometrial cancer in 1993 and was cured following surgery and adjuvant radiotherapy. However, in 2007, she developed multiple, erythematous, vaginal nodules that were eventually diagnosed as angiokeratoma of the vagina. The diagnosis of vaginal angiokeratoma may not be initially suspected. Therefore, physicians should perform a histologic examination to verify the condition and accordingly, provide relevant clinical management.

Bevacizumab, paclitaxel and carboplatin for advanced ovarian cancer: low risk of gastrointestinal and cardiovascular toxicity.

The purpose of this preliminary study was to retrospectively assess the incidence of bowel perforation and hypertension in two separate advanced ovarian cancer patient populations following first-line therapy, comprising paclitaxel, carboplatin and bevacizumab. The first 20 patients were treated with six cycles of paclitaxel (175 mg/m2), carboplatin (AUC of 5 i.v.), and bevacizumab (15 mg/kg of body weight); q21 days per an independent protocol. The subsequent patients (n = 12) were administered weekly paclitaxel (80 mg/m2), carboplatin (AUC of 5 i.v.) every four weeks, and bevacizumab (10 mg/kg of body weight) every two weeks for six cycles according to a separate, independent protocol. Bevacizumab was not added to either chemotherapy regimen until cycle 2. In both groups patients who achieved a complete response, partial response or stable disease at the conclusion of induction therapy received bevacizumab (10 mg/kg) and paclitaxel (135 mg/m2) q21 days as maintenance therapy. A total of 170 cycles (median = 6; range 3-6) of primary induction chemotherapy, 140 of which contained bevacizumab, were administered. Moreover, 206 cycles (median = 9; range 1-12) of maintenance chemotherapy have been delivered to 28 patients thus far. There was no incidence of GI perforation and only two patients demonstrated clinically significant hypertension. Previous studies involving bevacizumab have raised concerns regarding bowel perforations and hypertension. However, we did not encounter difficulties with either of these complications. While we recognize that the risk for bowel perforation remains in the 5-11% range, the study's preliminary results suggest that first-line treatment of advanced stage ovarian carcinoma with bevacizumab can be safely administered.

The utility and cost of routine follow-up procedures in the surveillance of ovarian and primary peritoneal carcinoma: a 16-year institutional review.

BACKGROUND: The purpose of this study was to evaluate the number of ovarian cancer and primary peritoneal cancer (PPC) progressive disease cases identified via routine follow-up procedures and the corresponding cost throughout a 16-year period at a single medical institution. METHODS: Previously undiagnosed epithelial ovarian (n=241), PPC (n=23), and concurrent ovarian and uterine (n=24) cancer patients were treated and then followed via CA-125, imaging (e.g., CT scan, chest X-ray), physical examination and vaginal cytology. RESULTS: In the group of 287 patients, there were 151 cases of disease progression. Serial imaging detected the highest number of progressive disease cases (66 initial and 45 confirmatory diagnoses), but the cost was rather high ($13,454 per patient recurrence), whereas CA-125 testing (74 initial and 20 corroborative diagnoses) was the least expensive ($3,924) per recurrent diagnosis. The total cost of surveillance during the 16-year period was nearly $2,400,000. CONCLUSION: Ultimately, serial imaging and the CA-125 assay detected the highest number of ovarian cancer and PCC progressive disease cases in comparison to physical examination and vaginal cytology, but nevertheless, all of the procedures were conducted at a considerable financial expense.

Marlex mesh mimicking an adnexal malignancy.

Hernia post-operative repair problems are infrequent and easily managed, but plug migration can be a more complicated event. Mesh plug migration is very uncommon and rarely presents as a suspected malignancy. We document a case involving a 79-year-old woman who exhibited a complex right-sided cystic mass that was presumed to be an adnexal malignancy. However, following surgery, the retroperitoneal mass was actually a PerFix mesh plug that migrated from an initial hernia surgery.

A phase II, multicenter trial of weekly topotecan in patients with recurrent platinum-sensitive epithelial cancers of the ovary and peritoneum.

The purpose of this study was to evaluate the response rate and toxicity of weekly topotecan in patients with recurrent platinum-sensitive epithelial cancers of the ovary and peritoneum. Thirty-nine platinum-sensitive recurrent ovarian cancer patients received topotecan (4 mg/m(2)) intravenously day 1, day 8, day 15, every 28 days. Colony-stimulating factors were excluded from the study. Clinical response was assessed by clinical, serologic, and radiographic measures at the conclusion of cycle four. Patients received 136 cycles of topotecan (median = 3; range 1-6) and were evaluated for response and toxicity. Median number of prior regimens was one. Grade 3/4 neutropenia developed in 3 (7.7%) patients. Grade 3 thrombocytopenia was seen in one (2.6%) patient, with no incidence of grade 4 thrombocytopenia. There was no evidence of grade 3 anemia, but one patient (2.6%) was associated with grade 4 anemia. There was no grade 3 or 4 neuropathy. We encountered 18 dose reductions following less than or equal to grade 2 myelosuppression, necessitating the removal of eight (20.5%) patients prior to cycle four. Twenty-one (53.8%) patients were removed from the study due to disease progression. Following the completion of cycle four, four (10.3%) patients demonstrated stable disease and four (10.3%) patients exhibited a partial response. There were no complete responses. Median disease-free survival was 12 weeks. Weekly topotecan (4 mg/m(2)) demonstrated modest activity and was moderately well tolerated. However, the significant number of dose reductions and high incidence of patients who demonstrated disease progression suggests additional modifications with this specific regimen are necessary.

Tuberculosis mimicking cervical carcinoma--case report.

Tuberculosis is a chronic bacterial infection that primarily results in pulmonary disease. Although there are several reported cases of extra-pulmonary tuberculosis, very few reports have described this disease in the female genital tract. We present a case involving a 67-year-old woman who presented with vaginal discharge, abdominal discomfort, and a pelvic mass in 2006. Clinically, cervical carcinoma was suspected, but pathologic diagnosis eventually revealed tuberculosis of the cervix. Tuberculosis is associated with a significant inflammatory reaction, which may mimic a gynecologic malignancy on exam or with diagnostic imaging. Despite the rare incidence, tuberculosis of the cervix should be considered in the differential diagnosis when cervical carcinoma is initially suspected.

A phase II study of outpatient first-line paclitaxel, carboplatin, and bevacizumab for advanced-stage epithelial ovarian, peritoneal, and fallopian tube cancer.

The purpose of this study was to assess the response rate and toxicity of paclitaxel, carboplatin, and bevacizumab (PCB) primary induction therapy for the treatment of advanced-stage ovarian carcinoma. Twenty patients were treated with paclitaxel (175 mg/m(2)), carboplatin (AUC of 5 IV), and bevacizumab (15 mg/kg) of body weight; q21 days for six cycles. Bevacizumab was administered at cycles two through six. Patients received 116 cycles of PCB chemotherapy (median = 6, range 2-6) and were evaluable for toxicity assessment. Grade 3 and 4 neutropenia developed in 23.3% and 25% of cycles, with no incidence of grades 3/4 thrombocytopenia or anemia. Prior to cycle six, one patient was removed from the study due to grade 3 neuropathy and another patient was excluded due to clinical deterioration. There was no incidence of gastrointestinal perforations, and only two patients demonstrated grade 3 hypertension (HTN). No grade 4 HTN was observed. Eighteen patients were evaluated for response following induction therapy. Six demonstrated a complete response (30%) and ten exhibited a partial response (50%), resulting in a total response rate of 80%. One patient exhibited stable disease (5%), and one demonstrated disease progression (5%). The lack of bowel perforations and wound complications should mitigate some concerns regarding these side effects. This study suggests that first-line treatment with PCB can be safely administered to previously untreated advanced-stage ovarian carcinoma patients. The favorable toxicity results and reasonable response rate warrant additional study in a larger patient population.

Surgery alone or surgery with a combination radiation or chemoradiation for management of patients with bulky-stage IB2 cervical carcinoma.

The management of stage IB2 cervical carcinoma remains controversial. This retrospective review evaluates 47 IB2 cervical carcinoma patients treated with surgery alone (S), surgery plus postoperative radiotherapy (SR), or surgery plus postoperative chemoradiation (SRC). Median progression-free interval (PFI) was 70.3 months for the SR group (n= 21), 73.3 months for the SRC group (n= 15), and 33.5 months for the S group (n= 11). The survival rate was 76% for the SR group, 87% for the SRC group, and 55% for the S group. Overall 5-year survival rate for the three groups was 75%. Median follow-up for the patient population was 61.3 months. The number of the patient and the nonrandomized nature of this study preclude any definitive conclusions, but interestingly, the SRC and SR groups exhibited a substantially better PFI and overall survival compared to the S group. Selection bias does not appear to be a factor since patients in SR or SRC group were at greater risk for recurrence (eg, higher incidence of deep stromal invasion, parametrial involvement) than patients in the S group; yet, they still experienced superior PFI and overall survival. Further studies comparing postoperative irradiation and chemoradiation with these patients in a randomized phase 3 trial may be warranted.

Spontaneous bacterial peritonitis following treatment for cervical carcinoma.

Spontaneous bacterial peritonitis (SBP) is an acute bacterial infection usually associated with ascites and cirrhosis or is a complication of peritoneal dialysis. There are very few case reports of cancer patients who developed this disease. Furthermore, there have been no published case reports of successfully treated gynecological cancer patients who later developed SBP. We present a case involving a 41-year-old woman who was treated for cervical carcinoma in 1992. She underwent radical surgery and adjuvant chemoradiation therapy. Two years later, the patient presented with streptococcal group B cellulitis associated with left leg lymphedema. She recovered following antibiotic treatment but had recurrent episodes of streptococcal cellulitis in her leg over the past 10 years. In 2003, the patient was admitted to the hospital because of sepsis, acute renal failure, and SBP. She was treated and recovered following treatment. SBP is usually associated with cirrhosis. Although SBP is rarely seen in successfully treated gynecological cancer patients, oncologists should be aware of this clinical entity. Timely treatment is essential to maximize chances of survival.

A phase I trial of a 3-day topotecan Q 21 days for recurrent epithelial cancers of the ovary, fallopian tube, and peritoneum.

OBJECTIVE: This trial was undertaken to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of topotecan that can be administered for 3 days q 21 days. A 3-day schedule is more convenient and less expensive than standard 5-day dosing. METHODS: Patients with recurrent epithelial ovary, tubal, or peritoneal carcinoma were treated with escalating doses of topotecan beginning at 2.50 mg/m(2) as an outpatient days 1-3 q 21 days. Colony stimulating factors were not employed prophylactically, but could be added for grade 4 marrow toxicity. RESULTS: Twenty patients with a median age of 61 (range 46-80) and performance status of 0 or 1 were entered. All patients had received at least one prior paclitaxel/platinum regimen; 6 had received two. Ninety-one cycles were delivered (median = 6) and 98.9% were on schedule. Grade 4 neutropenia was seen in 17 of 20 patients (85%) in cycle 1 and in 38 of 91 (41.8%) total cycles. Sixteen of 20 patients (80%) started G-CSF on cycle 2. Two of 91 (2.2%) cycles had grade 4 thrombocytopenia. Four cycles (4.4%) were associated with febrile neutropenia. Two patients experienced grade 4 neurotoxicity (DLT) at 4.25 mg/m(2). Other nonhematologic toxicity was mild. CONCLUSIONS: Topotecan can be safely administered on schedule as an outpatient days 1-3 q 21 days. Neurotoxicity was the DLT when G-CSF was added; the MTD was 3.75 mg/m(2). There was minimal other nonhematologic toxicity. Neutropenia was predictable and easily managed with G-CSF. Febrile neutropenia was uncommon and thrombocytopenia was rare at the doses evaluated.

Primary surgical cure of stage III-B cervical carcinoma with adnexal metastasis.

Management of patients with advanced stage cervical carcinoma remains suboptimal. Primary radiation therapy has been the standard treatment for years. Despite some changes in radiation technique, cure rates for advanced stage cervical cancer remain disappointing. Radiation complications in those patients can also be severe. We report here a case of a patient who presented with renal failure from bilateral ureteral obstruction from stage III-B cervical squamous carcinoma. The patient underwent a primary total pelvic exenteration with low rectosigmoid reanastomosis, urinary conduit construction, and cecal neovagina construction as definitive treatment. She was found to have metastasis to the broad ligament, ovary, and fallopian tube. Surgical margins and lymph nodes were negative. The patient did not receive any radiation therapy or chemotherapy. The patient is alive, healthy, and without evidence of disease 8 years following treatment.

"Medically necessary" panniculectomy to facilitate gynecologic cancer surgery in morbidly obese patients.

A retrospective review of patients in our practice who underwent abdominal panniculectomy to facilitate gynecologic cancer surgery was performed. The objective of the study was to determine if panniculectomy was a safe and useful procedure in the morbidly obese gynecologic cancer patient. A total of 12 patients underwent the procedure between 1992 and 1996. Optimal pelvic oncologic surgery was accomplished in all 12 patients. All aspects of those procedures were performed by gynecologic oncologists. The Buchwalter retractor was used in all cases. The patients' weights ranged from 170 to 429 pounds, with a mean of 275 pounds. The mean body mass index was 48, with a range from 37 to 67. Four patients had a history of diabetes mellitus. Nine patients healed without wound complications. Three patients developed superficial subcutaneous wound infections/necrosis that were successfully managed with office debridement. Abdominal panniculectomy is a reasonably safe procedure that makes radical pelvic surgery possible regardless of the patient's weight. Prolonged wound bulb suction drainage may decrease the incidence of wound necrosis/infection in these high-risk patients.

Single-dose dexamethasone paclitaxel premedication.

Paclitaxel is one of the most active chemotherapy agents for the treatment of ovarian and other gynecologic cancers. Hypersensitivity reactions (HSR) remain one of the major clinical concerns in the use of paclitaxel. This report deals with 183 consecutive patients treated with paclitaxel chemotherapy. A total of 1010 cycles were administered. Premedication consisted of single-dose intravenous decadron, benadryl, and cimetidine administered immediately prior to chemotherapy. Four hypersensitivity reactions occurred. All patients recovered uneventfully from these reactions. Two of these patients received additional oral decadron followed by the standard premedication and were successfully retreated with multiple courses of paclitaxel therapy without reaction. Our findings confirm other reports that paclitaxel chemotherapy hypersensitivity reactions can be decreased with a single-dose intravenous decadron premedication regimen and that patients who do have paclitaxel HSRs may be safely retreated with paclitaxel.

Three-hour paclitaxel infusion and carboplatin is an effective outpatient treatment for stage III epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to determine the response rate and toxicity of a 3-h paclitaxel infusion and carboplatin delivered as outpatient therapy for the treatment of stage III/IV epithelial ovarian cancer. METHODS: Thirty patients with stage III/IV epithelial ovarian cancer underwent cytoreductive surgery. The first 10 patients received adjuvant paclitaxel 150 mg/m2 via 3-h infusion on day 1 and carboplatin 5 times area under the curve on day 2 (group 1) every 28 days. The paclitaxel dose was escalated to 175 mg/m2 for the next 20 patients (group 2). chi 2 and Kaplan-Meier procedures were used for statistical analysis. RESULTS: Nine of 51 cycles in group 1 (17.6%) and 19 of 116 cycles (16.4%) in group 2 were associated with grade 4 neutropenia (P = 0.96), but only 2 of the 161 total cycles (0.01%) had fever and neutropenia. One patient in group 1 experienced grade 3 thrombocytopenia. Two patients in the entire group (7.4%) required colony-stimulating factors. One patient in group 2 (3.7%) had grade 3 neurotoxicity. With a median follow-up of 29 months for the entire group, 5 of 8 patients (62.5%) in group 1 and 14 of 19 patients (73.7%) in group 2 are alive. Median progression-free survival for group 1 and 2 is 13 and 14 months, respectively. Median overall survival has not been reached. CONCLUSIONS: Paclitaxel via 3-h infusion and carboplatin is an effective outpatient treatment for epithelial ovarian cancer that can be safely administered on schedule in the majority of patients.

Topical podofilox for the treatment of condylomata acuminata in women.

The purpose of this study was to determine the efficacy and safety of 0.5% podofilox solution (Condylox) for the treatment of genital warts in women. Thirty-seven women with anogenital warts applied the solution to the surface of these warts twice daily for 3 days, followed by 4 drug-free days. A minimum of two and a maximum of four treatment cycles were given. The subjects were evaluated weekly for the first 4 weeks and again at 6 and 10 weeks. At the end of 10 weeks, the mean number of warts per patient was reduced from 6.27 to 1.1, and half of the patients were completely cleared of warts. Only eight of 37 subjects (21.6%) developed new warts during the study period. Approximately 15% of patients reported "severe" local reactions to the treatment after the first treatment cycle, but this was reduced to only 5% by the last treatment cycle. During the same period, the patients reporting no side effects increased from 44 to 86%. The only woman who discontinued the study did so because of dizziness and epigastric discomfort, probably unrelated to drug use. Thus, 0.5% podofilox solution appears to be an effective treatment for condylomata acuminata, with acceptable side effects that are local and temporary.

Whole-abdominal radiotherapy for patients with minimal residual epithelial ovarian cancer.

Sixteen patients with advanced epithelial ovarian cancer who were treated with cytoreductive surgery followed by multiagent chemotherapy were found to have residual tumor masses less than 2 cm in greatest diameter at reexploration and were treated with whole-abdominal radiation (19-31 Gy). Thirteen patients also received pelvic boosts to a total pelvic dose of 41-53.7 Gy. Radiotherapy was completed in all but 2 patients after treatment delays in 7 patients. Early treatment complications included myelosuppression in 11 patients, diarrhea in 3, and a self-limited small bowel obstruction in one. Delayed complications were severe and included 9 patients with radiation enterocolitis, 8 of whom required intestinal resection or diversion. One additional patient with radiation cystitis required instillation of formalin to control bleeding. Two patients are without evidence of disease 28 and 30 months following radiotherapy, while the remaining 14 patients have recurred after a median progression-free interval of 9 months (range 1-30 months). All patients who recurred failed within the treatment field and died of cancer after a median interval of 19 months following radiotherapy and 9 months after documentation of progression. These data suggest that few patients with persistent ovarian cancer following surgery and chemotherapy will be salvaged with radiotherapy.